Δ-8-tetrahydrocannabinol from cannabidiol extracted from hemp

ABSTRACT

The present invention describes a process to isomerize industrial hemp derived Cannabidiol (CBD) to a pure Δ8-tetrahydrocannabinol (Δ8-THC) extract. This procedure will produce Δ8-tetrahydrocannabinol that is essentially free from any detectable levels of Δ9-tetrahydrocannabinol (Δ9-THC). Included in this filing are methods and processes to scale the reaction from the lab to process to large scale manufacturing. Additionally, the resulting extract from said methods and processes consists of higher purity than previously reported in the art and greater efficiency compared to prior art.

FIELD OF THE INVENTION

The invention relates to the field of cannabinoid synthesis, and inparticular the chemical processes for making Δ8-tetrahydrocannabinolfrom cannabidiol extract of industrial hemp having less than 0.3%Δ9-tetrahydrocannabinol using processes that do not permit isomerizationof cannabidiol to Δ9-tetrahydrocannabinol to maintain compliance withfederal laws throughout processing, and using a differentialdistillation using vacuum distillation for volatile or low temperatureimpurities and wipe film distillation to remove high temperatureimpurities.

BACKGROUND OF THE INVENTION

Cannabinoids are an important class of diverse compounds that connectwith brain receptors which are part of the endocannabinoid system. Thisseries of receptors modulates homeostasis throughout the various facetsof the human body. The most well-known receptors are the CB1 and CB2that interact with the central nervous system and immune systemrespectively. There are over 100 naturally occurring cannabinoids witheach affecting the body in specific ways and helping to alleviate avariety of conditions. The cannabinoid discussed in this application,Δ8-tetrahydrocannabinol, has shown great promise in promoting a generalstate of well-being in the user. According to The National CancerInstitute, Δ8-tetrahydrocannabinol is defined as “an analogue ofΔ9-tetrahydrocannabinol with antiemetic, anxiolytic,appetite-stimulating, analgesic and neuroprotective properties.”

Δ8-tetrahydrocannabinol has a lower psychotropic potency thanΔ9-tetrahydrocannabinol which may further aid in its acceptance as amedicinal based cannabinoid. Additionally, Δ8-tetrahydrocannabinol bindsto both the CB1 and CB2 receptors. CB1 receptors are found in thecentral nervous system, mainly in the spinal cord and brain. CB2receptors are found on cells primarily associated with the immune systemand are more broadly distributed, therefore influencing most of thebody. Since Δ9-tetrahydrocannabinol predominantly interacts with the CB1receptor, it has a more limited medicinal spectrum than that ofΔ8-tetrahydrocannabinol. Lastly, Δ8-tetrahydrocannabinol has shown areduction of side effects compared to Δ9-tetrahydrocannabinol withpatients reporting much less paranoia and lethargy from its use.

Webster, Sarna, and Mechoulam (U.S. Pat. No. 7,399,872) describe amethod for producing Δ8-tetrahydrocannabinol where they achieved an 81%yield of 86% Δ8-tetrahydrocannabinol as detected by High PerformanceLiquid Chromatography (HPLC). This method produces small amounts ofΔ9-tetrahydrocannabinol which means that further purification by liquidchromatography is necessary to obtain a purified Δ8-tetrahydrocannabinolproduct. Our method improves quite significantly on the overall purityand yield of the Δ8-tetrahydrocannabinol in a single step reaction.Mechoulam and Abrahamov (U.S. Pat. No. 5,605,928) also detailsΔ8-tetrahydrocannabinol's antiemetic effects on children. Eight childrenwere given a dose of Δ8-tetrahydrocannabinol before chemotherapytreatment and it was shown to effectively eliminate all vomiting withlittle to no side effects. Δ8-tetrahydrocannabinol has been shown to be200% more effective as an anti-emetic than Δ9-tetrahydrocannabinol andhas been especially helpful when used as an anti-emetic in children.(Abrahamov et al, 1995, Life Sciences 56: 2097-2102).

The Farm Bill of 2018 gave farmers in the United States the opportunityto grow industrial hemp on a nationwide basis. Due to many of thecultivars being high in Cannabidiol, there was major interest incultivation for biopharmaceutical applications. After harvest,industrial hemp is typically processed using solvent such as ethanol,carbon dioxide, or hydrocarbon extraction to create a full spectrumextract. Further purification occurs through distillation and isolationof the Cannabidiol to increase potency and purity of the end product.The Farm Bill of 2018 states that hemp is defined as “the plant Cannabissativa L.” and any part of that plant, including the seeds thereof andall derivatives, extracts, cannabinoids, isomers, acids, salts, andsalts of isomers, whether growing or not, with a delta-9tetrahydrocannabinol concentration of not more than 0.3 percent on a dryweight basis.” Given the large supply of industrial hemp and Cannabidiolin the United States, there exists a need to work towards using thiscannabinoid more widely to produce other medicinally beneficialcompliant compounds.

SUMMARY OF THE INVENTION

The inventive process starts with an industrial hemp plant that is lessthan 0.3% Δ9-THC. The cannabidiol (CBD) extract obtained from thecompliant (verified less than 0.3% Δ9-THC) hemp is processed to alsohave less than 0.3% Δ9-THC. The next step of processing with an organicacid, e.g. p-toluenesulfonic acid, in a chemically-related andcompatible solvent, e.g. toluene, followed by quenching with a weakbase, e.g. sodium bicarbonate, and washing with water, also yields acrude Δ8-THC oil having less than 0.3% Δ9-THC. Thus, the entire Δ8-THCprocess stays Δ9-THC-compliant at each step. Further performing ashort-path vacuum distillation to remove the low temperature impuritiesensures that the crude Δ8-THC oil produces a Δ8-THC distillate withoutallowing cannabidiol to isomerize to the unwanted and non-compliantΔ9-THC. Lastly, performing a wiped film distillation to remove the hightemperature impurities also ensures that the Δ8-THC distillate producesa highly pure Δ8-THC oil having >99% Δ8-THC by HPLC without allowing anyfurther isomerization to the unwanted and non-compliant Δ9-THC.

The invention also includes compositions and formulations containing theΔ8-THC oil having >99% Δ8-THC by HPLC.

BRIEF DESCRIPTION OF THE FIGS

FIG. 1 is an HPLC graph showing the peaks of various cannabinoids.

FIG. 2 is a process flowchart showing one preferred embodiment of theinventive process described and claimed herein for obtaining a crudeΔ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than 0.3%Δ9-THC by HPLC.

FIG. 3 is a process flowchart showing another preferred embodiment ofthe inventive process described and claimed herein for obtaining a crudeΔ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than 0.3%Δ9-THC by HPLC and then performing vacuum distillation of the crudeΔ8-THC oil with a short path vacuum distillation system to obtain aclear Δ8-THC distillate, followed by a wiped film distillation of theclear Δ8-THC distillate to obtain a Δ8-THC oil having >99% Δ8-THC byHPLC.

FIG. 4 is a process flowchart showing another preferred embodiment ofthe inventive process described and claimed herein for obtaining a crudeΔ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than 0.3%Δ9-THC by HPLC and then performing vacuum distillation of the crudeΔ8-THC oil with a short path vacuum distillation system to obtain aclear Δ8-THC distillate, followed by a wiped film distillation of theclear Δ8-THC distillate to obtain a Δ8-THC oil having >99% Δ8-THC byHPLC, followed by repeating the wiped film distillation a second time.

FIG. 5 is a process flowchart showing yet another preferred embodimentof the inventive process described and claimed herein for obtaining acrude Δ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than0.3% Δ9-THC by HPLC, and verifying the crude Δ8-THC oil compliance ofless than 0.3% Δ9-THC using post decarboxylation and/or HPLC.

FIG. 6 is a process flowchart showing another preferred embodiment ofthe inventive process described and claimed herein for obtaining a crudeΔ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than 0.3%Δ9-THC by HPLC, verifying the crude Δ8-THC oil compliance of less than0.3% Δ9-THC using post decarboxylation and/or HPLC, then performingvacuum distillation of the crude Δ8-THC oil with a short path vacuumdistillation system to obtain a clear Δ8-THC distillate, followed by awiped film distillation of the clear Δ8-THC distillate to obtain aΔ8-THC oil having >99% Δ8-THC by HPLC, verifying the clear Δ8-THCdistillate and/or Δ8-THC oil compliance of less than 0.3% Δ9-THC usingpost decarboxylation and/or HPLC, optionally followed by repeating thewiped film distillation a second time.

FIG. 7 is a process flowchart showing another preferred embodiment ofthe inventive process described and claimed herein for obtaining a crudeΔ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than 0.3%Δ9-THC by HPLC, then performing vacuum distillation of the crude Δ8-THCoil with a short path vacuum distillation system to obtain a clearΔ8-THC distillate, followed by a wiped film distillation of the clearΔ8-THC distillate to obtain a Δ8-THC oil having >99% Δ8-THC by HPLC,optionally followed by repeating the wiped film distillation a secondtime, and verifying compliance of less than 0.3% Δ9-THC of the crudeΔ8-THC oil, the clear Δ8-THC distillate and/or Δ8-THC oil using averification method selected from the group consisting of postdecarboxylation, HPLC, gas chromatography (GC), GC coupled with massspectrometry (MS), GC coupled with flame ionization detection (FID),HPLC with MS, HPLC with ultraviolet (UV) absorbance, HPLC with diodearray detection (DAD), HPLC-electrospray ionization-quadrupole time offlight (ESI-qTOF), HPLC-MS/MS, ultra-performance liquid chromatography(UPLC), UPLC-qTOF, matrix assisted laser desorption ionization massspectrometry (MALDI-MS), thin layer chromatography (TLC), Fouriertransform infrared spectroscopy (FTIR), and nuclear magnetic resonancespectrometry (NMR).

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to the field of cannabinoid synthesis. Morespecifically, the process described covers industrial scaleisomerization of Cannabidiol (CBD) into an essentially pureΔ8-tetrahydrocannabinol (Δ8-THC) extract. The chemical processes hereinprovides for making Δ8-tetrahydrocannabinol from cannabidiol extract ofindustrial hemp having less than 0.3% Δ9-tetrahydrocannabinol usingprocesses for obtaining Δ8-THC that do not permit isomerization ofcannabidiol to Δ9-tetrahydrocannabinol to maintain compliance withfederal laws throughout processing, and using a differentialdistillation using vacuum distillation for volatile or low temperatureimpurities and wipe film distillation to remove high temperatureimpurities.

Essentially pure is defined as greater than 99% presence ofΔ8-tetrahydrocannabinol on a weight to weight basis as detected by HPLC.Such purity of Δ8-tetrahydrocannabinol is generally accepted as apharmaceutical, nutraceutical, skin care and/or cosmetic compositions.Additionally, the method consists of the ability not only to producehigh purity Δ8-tetrahydrocannabinol (i.e. 90% to 99.9%) but also toscale up from converting hundreds of grams of CBD to the ability toconvert hundreds of kilograms of CBD while maintaining said highΔ8-tetrahydrocannabinol (i.e. 90% to 99.9%). In essence the purity ofsaid Δ8-tetrahydrocannabinol is considered essentially pure (i.e. 90% to99.9%) on a weight to weight percent basis of the total composition.

Stated herein are the preferred and alternative methods for convertingCBD to Δ8-THC. The reaction mixture can be manipulated by time,temperature, and catalyst concentration to produce extracts at differentpurities depending on the goal of the reaction.

Provided herein is a method of converting CBD to an essentially pureΔ8-THC with potency greater than 99%. This process is completed byintroducing Cannabidiol from industrial hemp and adding it to a specificorganic solvent with a specific catalyst to form a reaction mixture,loading the mixture into a reaction vessel, heating the solution to thepreferred temperature, allowing it to reflux for the preferred duration,quenching the reaction mixture when complete, removing the aqueousphase, recovering the solvent, stripping the terpenes and distilling thecrude residue to form a pure Δ8-THC extract.

PREFERRED EMBODIMENTS

In a preferred embodiment, as shown in FIG. 2 , the invention relates toa process, having the steps of:

-   -   (i) refluxing a cannabidiol extract from industrial hemp having        less than 0.3% Δ9-THC in a mixture of toluene and        p-toluenesulfonic acid at about 70° C.-100° C. for about        120-1440 minutes to obtain a reaction mixture having less than        0.3% Δ9-THC; and    -   (ii) adding aqueous sodium bicarbonate to neutralize the        reaction mixture, adding water, and evaporating to obtain a        crude Δ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and        less than 0.3% Δ9-THC by HPLC.

In another preferred embodiment, as shown in FIG. 3 , the inventionprovides a process as described wherein the p-toluenesulfonic acid isabout 0.12-0.598% (w/w) and the cannabidiol extract starting material isabout 23% (wt/wt).

In another preferred embodiment, as shown in FIG. 3 , the inventionprovides a process as described, comprising the additional steps of:

-   -   (iii) Vacuum distilling the crude Δ8-THC oil with a short path        vacuum distillation system until a clear Δ8-THC distillate        starts to condense and then immediately stopping the vacuum        distilling, wherein said vacuum distilling removes residual        solvent and volatile cannabidiol impurities from the clear        Δ8-THC distillate; and    -   (iv) Wiped film distilling the clear Δ8-THC distillate with a        wiped film distillation unit to obtain a Δ8-THC oil having >99%        Δ8-THC by HPLC, wherein said wiped film distilling removes high        temperature cannabinoid impurities having a non-vacuum boiling        higher than 180° C.

In another preferred embodiment, as shown in FIG. 4 , the wiped filmdistilling is performed twice.

Any of the preferred embodiments herein may include wherein the sourceof cannabidiol extract is selected from the group consisting of CBDcrude, CBD distillate, and CBD isolate, and wherein the mixture isrefluxed at 70° C. for 120 minutes, the aqueous sodium bicarbonate is10% NaHCO₃, and the crude Δ8-THC oil is 91.68%-99.73% Δ8-THC by HPLC.

Any of the preferred embodiments herein may include wherein the mixtureincludes a second organic solvent selected from the group consisting ofdichloromethane, dichloroethane, ethanol, cyclohexane, hexanes,heptanes, and a combination thereof, and wherein the mixture includes asecond catalyst selected from the group consisting of Zinc Chloride,Hydrochloric acid, Sulfuric acid, Zinc Bromide, Boron Trifluoride, BoronTrifuluoride Diethyl Ethereate, and a combination thereof.

In a preferred embodiment, the invention includes a process of producingΔ8-tetrahydrocannabinol (Δ8-THC), comprising providing a source ofCannabidiol extract, adding a catalyst and organic solvent to create areaction mixture, refluxing the reaction mixture for a specified timeunder acidic conditions, neutralizing the reaction, recovering a solventproduct, and distilling the solvent product to obtain a crude Δ8-THC oilhaving >99% purity.

Any of the preferred embodiments herein may include a method wherein therefluxing is selected from the group consisting of a broad refluxperformed for between 0.5 to about 48 hours, a medium range refluxperformed for between 60 to 180 min, and a specific reflux performed forapproximately 120 min., and wherein the resulting crude Δ8-THC oil isfurther purified using fractional, vacuum, short path, molecular, and/orwiped film distillation.

Any of the preferred embodiments herein may include wherein the dilutionratio of the Cannabinoid extract to the organic solvent is 3 to 6 on aweight basis.

Any of the preferred embodiments herein may include wherein the sourceCannabidiol extract is CBD crude, CBD isolate or CBD distillate, whereinthe organic solvent is toluene, wherein the catalyst is 2.6% ofp-toluenesulfonic acid monohydrate, and wherein the refluxing isperformed for between 60 to 180 minutes at a reaction temperatureselected from the group consisting of a range between 50 to 100° C., arange between 60° C. to 80° C., and approximately 70° C.

Any of the preferred embodiments herein may include wherein the crudeΔ8-THC having >99% purity is eluted with a second solvent or solventmixture and separated from Δ9-THC on a Normal Phase HPLC column or aReverse Phase HPLC column, following washing the column with the secondsolvent or solvent mixture, wherein the second solvent or solventmixture is selected from toluene, ether in petroleum ether, andwater-acetonitrile, wherein the eluting solvent or solvent mixture isthe same as the washing solvent or solvent mixture.

Any of the preferred embodiments herein may include wherein the organicsolvent consists essentially of dichloromethane, dichloroethane,ethanol, cyclohexane, hexanes, heptanes, toluene, and a combinationthereof.

Any of the preferred embodiments herein may include wherein the catalystis selected from the group consisting of Zinc Chloride or Hydrochloricacid or Sulfuric acid or Zinc Bromide or Boron Trifluoride or BoronTrifluoride Diethyl Ethereate, p-toluenesulfonic acid monohydrate, and acombination thereof.

Any of the preferred embodiments herein may include wherein the acidicreaction mixture is neutralized using a quenching agent followed byaddition of purified water, the quenching agent selected from the groupconsisting of sodium carbonate, sodium bicarbonate, sodium sulfate,sodium thiosulfate, a 10% NaHCO₃ solution, and a combination thereof.

In another preferred embodiment, the invention provides a process,comprising: (i) dissolving 5 kg to 500 kg of CBD isolate with 25 to 250liters of toluene to form a solution; (ii) loading the solution into areaction vessel and heating; (iii) adding p-toluenesulfonic acidmonohydrate (100 to 2 kg) to the reaction vessel and refluxing at 60-80°C. for 100-150 minutes; (iv) quenching the mixture with aqueous 10%NaHCO₃, and then adding purified water; (v) evaporating the mixture tocollect a crude oil having greater than 90% Δ8-THC; (vi) loading thecrude oil into a short path vacuum distillation system having Raschigrings in a condensing head and heating to remove residual solvent andterpenes and obtain a clear distillate; (vii) loading the cleardistillate into a wiped film distillation unit and collecting adistilled oil having greater than 99% Δ8-tetrahydrocannabinol (Δ8-THC).

Any of the preferred embodiments herein may include a pharmaceuticalcomposition comprising the Δ8-THC made according to the processes hereinand a pharmaceutically acceptable carrier, wherein the pharmaceuticalcomposition is a topical formulation or a nutraceutical formulation.

Any of the preferred embodiments herein may include a process,comprising: dissolving a quantity of CBD isolate in toluene to form asolution; loading the solution into a reaction vessel and heating;adding p-toluenesulfonic acid monohydrate to the reaction vessel andrefluxing at 60-80° C. for 100-150 minutes; quenching the mixture withaqueous 10% NaHCO₃, and then adding purified water; evaporating themixture to collect a crude oil having greater than 90% Δ8-THC; loadingthe crude oil into a short path vacuum distillation system havingRaschig rings in a condensing head and heating to remove residualsolvent and terpenes and obtain a clear distillate; loading the cleardistillate into a wiped film distillation unit and collecting adistilled oil having greater than 99% Δ8-tetrahydrocannabinol (Δ8-THC).

Any of the preferred embodiments herein may include an organic solventthat comprises cyclohexane, ethanol, methanol, isopropanol, acetone,toluene, hexane, pentane, heptane, methylene chloride (dichloromethane),ethylene dichloride (dichloroethane), tetrahydrofuran, benzene,chloroform, purified water, diethyl ether, and/or xylene.

In a preferred embodiment, the organic solvent is toluene.

Any of the preferred embodiments herein may include catalyst that may bea Lewis and/or Bronsted Lowry acid comprising acetic acid, ascorbicacid, citric acid, hydrochloric acid, hydrogen chloride, phosphoricacid, sulfuric acid, p-toluenesulfonic acid, p-toluenesulfonic acidmonohydrate, zinc chloride, zinc bromide, zinc iodide, tin chloride, tinbromide, tin iodide, magnesium chloride, magnesium bromide, magnesiumiodide, silver chloride, silver bromide, silver iodide, borontrifluoride, or boron trifluoride diethyl etherate,

In a preferred embodiment, the catalyst is p-toluenesulfonic acidmonohydrate.

In some embodiments, the catalyst may be an activated powder comprisingof activated carbon, bentonite clay, and/or bleaching clay.

In some embodiments, the reaction mixture is filtered before beingloaded into the evaporation equipment by activated carbon, bentoniteclay, bleaching clay, silica, diatomaceous earth, celite, and/ormag-sil.

In some embodiments, the reaction mixture is neutralized with coldwater, another alkali metal hydrogen carbonate or a carbonate of analkali metal.

In some embodiments the reaction mixture is stirred at room temp,stirred while being heated or stirred while being chilled.

In some embodiments Cannabidiol (CBD) isolate, distillate, crude can beused.

In some embodiments the reaction can be carried out under inertatmosphere with argon, nitrogen, and/or equivalent gas.

Any of the process embodiments herein may include a step of verifyingcompliance of less than 0.3% Δ9-THC of the crude Δ8-THC oil.

Any of the process embodiments herein may include a step of verifyingcompliance of less than 0.3% Δ9-THC of the crude Δ8-THC oil, andcomprising another step of verifying compliance of less than 0.3% Δ9-THCof the clear Δ8-THC distillate and/or Δ8-THC oil.

Any of the embodiments herein may include a process for obtaining acrude Δ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than0.3% Δ9-THC by HPLC, then performing vacuum distillation of the crudeΔ8-THC oil with a short path vacuum distillation system to obtain aclear Δ8-THC distillate, followed by a wiped film distillation of theclear Δ8-THC distillate to obtain a Δ8-THC oil having >99% Δ8-THC byHPLC, optionally followed by repeating the wiped film distillation asecond time, and including the step of verifying compliance of less than0.3% Δ9-THC of the crude Δ8-THC oil, the clear Δ8-THC distillate and/orΔ8-THC oil using a verification method selected from the groupconsisting of post decarboxylation, HPLC, gas chromatography (GC), GCcoupled with mass spectrometry (MS), GC coupled with flame ionizationdetection (FID), HPLC with MS, HPLC with ultraviolet (UV) absorbance,HPLC with diode array detection (DAD), HPLC-electrosprayionization-quadrupole time of flight (ESI-qTOF), HPLC-MS/MS,ultra-performance liquid chromatography (UPLC), UPLC-qTOF, matrixassisted laser desorption ionization mass spectrometry (MALDI-MS), thinlayer chromatography (TLC), Fourier transform infrared spectroscopy(FTIR), and nuclear magnetic resonance spectrometry (NMR).

General Definitions

The embodiments herein and the various features and advantageous detailsthereof are explained more fully with reference to the non-limitingembodiments that are illustrated in the accompanying drawings anddetailed description. Descriptions of well-known components andprocessing techniques are omitted so as to not unnecessarily obscure theembodiments herein. The examples used herein are intended merely tofacilitate an understanding of ways in which the embodiments herein maybe practiced and to further enable those of skill in the art to practicethe embodiments herein. Accordingly, the examples should not beconstrued as limiting the scope of the embodiments herein.

Rather, these embodiments are provided so that this disclosure will bethorough and complete, and will fully convey the scope of the inventionto those skilled in the art. Like numbers refer to like elementsthroughout. As used herein the term “and/or” includes any and allcombinations of one or more of the associated listed items.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to limit the full scope of theinvention. As used herein, the singular forms “a”, “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise. It will be further understood that the terms“comprises” and/or “comprising,” when used in this specification,specify the presence of stated features, integers, steps, operations,elements, and/or components, but do not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components, and/or groups thereof.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art. Nothing in this disclosure is to be construed as anadmission that the embodiments described in this disclosure are notentitled to antedate such disclosure by virtue of prior invention. Asused in this document, the term “comprising” means “including, but notlimited to.”

Many modifications and variations can be made without departing from itsspirit and scope, as will be apparent to those skilled in the art.Functionally equivalent methods and apparatuses within the scope of thedisclosure, in addition to those enumerated herein, will be apparent tothose skilled in the art from the foregoing descriptions. Suchmodifications and variations are intended to fall within the scope ofthe appended claims. The present disclosure is to be limited only by theterms of the appended claims, along with the full scope of equivalentsto which such claims are entitled. It is to be understood that thisdisclosure is not limited to particular methods, reagents, compounds,compositions or biological systems, which can, of course, vary. It isalso to be understood that the terminology used herein is for thepurpose of describing particular embodiments only, and is not intendedto be limiting.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art thatvirtually any disjunctive word and/or phrase presenting two or morealternative terms, whether in the description, claims, or drawings,should be understood to contemplate the possibilities of including oneof the terms, either of the terms, or both terms. For example, thephrase “A or B” will be understood to include the possibilities of “A”or “B” or “A and B.”

In addition, where features or aspects of the disclosure are describedin terms of Markush groups, those skilled in the art will recognize thatthe disclosure is also thereby described in terms of any individualmember or subgroup of members of the Markush group.

As will be understood by one skilled in the art, for any and allpurposes, such as in terms of providing a written description, allranges disclosed herein also encompass any and all possible subrangesand combinations of subranges thereof. Any listed range can be easilyrecognized as sufficiently describing and enabling the same range beingbroken down into at least equal subparts. As will be understood by oneskilled in the art, a range includes each individual member.

Specific Definitions

The terms Delta-8-THC or Δ8-tetrahydrocannabinol or Δ8-THC refers to6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol(IUPAC 2019-06). Delta-8-THC can be represented by 2D structure asfollows:

The term delta-9-THC or Δ9-tetrahydrocannabinol or Δ9-THC refers to(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol(IUPAC 2019-06). Delta-9-THC can be represented by 2D structure asfollows:

The term “pure” or “essentially pure” or “highly pure” refers to greaterthan 99% of Delta-8-THC in a given final product. Purity may be obtainedusing HPLC.

FIG. 1 illustrates, using an HPLC chromatograph, the peaks of variouscannabinoids. The first to come off at around 90 seconds iscannabidivarinic acid, followed by cannabidivarin at around 1′45″. Thenext peaks, 3-4-5-6-7, fall between 2 minutes and 3 minutes (2′-3′) arecannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, andtetrahydrocannabivarin, respectively. Between 4′ and 5′, the peaks for 8and 9 are shown for tetrahydrocannabivarinic acid, and cannabidiol(CBD). Between 6′ and 7′, the peaks for 10 and 11 areDelta-9-tetrahydrocannabinol (D9-THC), and Delta-8-tetrahydrocannabinol(D8-THC). At around the 9 minute (9′) mark the number 12 and 13 speciesare cannabichromene and Delta-9-tetrahydrocannabinolic acid A. Andfinally at about 11′30″, the cannabichromenic acid comes off.

The term “CBD” refers to cannibidiol and has a molecular weight of314.47 g/mol.

The term “CBD Distillate” refers to the process of applying high heat(boiling point) to raw extracted oil in a distillation chamber toseparate the oil components and obtain highly pure CBD. CBD distillatedoes not contain or contains only a very small percentage of terpenes.

The term “CBD Isolate” refers to 99% pure CBD created by cooling andcrystallizing CBD extract to form a white powder

The term “hemp” does not include marijuana, and “natural hemp”,“industrial hemp”, or “hemp” as used herein refers to a variety ofCannabis sativa that contains less than 0.3%Delta-9-tetrahydrocannabinol (THC).

The term “cannabinoid” or “cannabinoids” as used herein encompasses atleast the following substances: Δ-8 tetrahydrocannabinol,Δ-9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD),cannabigerol (CBG), Δ-9(11)-tetrahydrocannabinol (exo-THC),cannabichromene (CBC), tetrahydrocannabinol-C3 (THC-C3),tetrahydrocannabinol{circumflex over ( )} (THC-C4).

Examples of cannadinoids include:

Δ8-THC has a published boiling point at about 177° C. Δ9-THC has apublished boiling point at about 157° C. Solvents, non-compliantcannabinoids, and volatile cannabinoids are defined as having a boilingpoint less than about 160° C. In distillation, as used herein, these lowtemperature compounds are known as “heads”. High boiling pointcannabinoids (vacuum) are defined herein as cannabinoids having aboiling point above about 180° C., and do not include, by definitionΔ8-THC. In distillation, as used herein, these high temperaturecompounds are known as “tails”, with the “main” being Δ8-THC, its crudeoils, its distillates, and its purified oils.

Boiling points differ among cannabinoids. This permits separation bydistillation techniques.

TABLE Relevant cannabinoid structures and boiling points STRUCTURE NAMEB.P.

Δ-9-THC Δ-9-tetrahydrocannabinol 390.4° C. ± 42.0° C. at 760 mmHg; 157°C. under vacuum

CBD cannabidiol 463.9° C. ± 45.0° C. at 760 mmHg; 160-180° C. undervacuum

Δ-8-THC Δ-8-tetrahydrocannabinol 383.5° C. ± 42.0° C. at 760 mmHg;175-178° C. under vacuum

TABLE Cannabinoid b.p. - lowest to highest, under vacuum NAME B.P. ° C.THCA 105 CBG 105 B-CARYOPHYLLENE 119 p-CYMENE 134 a-PINENE 156 D9-THC157 CBD 160-180 B-MYRCENE 166-168 D8-THC 175-178 1,8-CINEOLE 176d-LIMONENE 177 CBC 185 CBN 185 LINALOOL 198 TERPINEOL-4-OL 209a-TERPINEOL 218 THCV 220 PULEGONE 224 APIGENIN 270 QUERCETIN 302 CBDA316-531 B-SITOSTEROL 414

The term “extraction” refers to a process for obtaining raw Cannabinoidextract from dried Hemp plant material. Non-limiting illustrativeprocesses include CO2 extraction, liquid chromatography, solventextraction, and olive oil extraction. Extracts contain other plantcomponents—major and minor cannabinoids, terpenes, and flavonoids—thatisolates do not.

The term “CO2 extraction” refers to a process for obtaining CBD fromindustrial hemp that comprises by way of illustration in a non-limitingexample the following steps: —extraction with supercritical CO2 (e.g.60° C., 250 bar); —decarboxylation (e.g. 80° C., 2 hours); and—separation in a high pressure column (using CO2 as solvent). The methodis shown to yield an extract containing CBD in approximately 90% purity.

The term “Winterization” refers to combining extracted CBD oil withethanol and freezing overnight, which is then filtered to remove fatsand other impurities, and the filtrate is heated to evaporate theethanol.

The term “organic solvent” refers to ethanol, methanol, isopropanol,acetone, toluene, hexane, pentane, heptane, methylene chloride(dichloromethane), ethylene dichloride (dichloroethane),tetrahydrofuran, benzene, chloroform, purified water, diethyl ether,and/or xylene. In a preferred embodiment, the organic solvent istoluene.

The term “catalyst” refers to a Lewis and/or Bronsted Lowry acidcomprising hydrochloric acid, hydrogen chloride, phosphoric acid,sulfuric acid, p-toluenesulfonic acid, p-toluenesulfonic acidmonohydrate, zinc chloride, zinc bromide, zinc iodide, tin chloride, tinbromide, tin iodide, magnesium chloride, magnesium bromide, magnesiumiodide, silver chloride, silver bromide, silver iodide, borontrifluoride, or boron trifluoride diethyl etherate, In a preferredembodiment, the catalyst is p-toluenesulfonic acid monohydrate.

The term “Short Path Distillation” refers to slowly heating CBD oiluntil extraneous substances having a different boiling point than CBD,such as heads (terpenes and high volatiles), and tails (high boilingpoint cannabinoids), are vaporized into a distillation tube, condensedby cooling coils, and separated, leaving purified CBD oil. Short Pathdistillation is generally not known for scalability into large batches.Short path distillation produces a high-quality distillate, but islimited in scale.

Short path distillation utilizes an apparatus with a multi-positionreceiver and condensing head. This process is very limited in scale andproduction, but can produce high-quality distillate with an experiencedoperator. Crude oil is heated in a boiling ask with a magnetic stirrer.The condensing head is jacketed and requires a recirculating chiller tocool the condensing head to condense the cannabinoid vapor back into aliquid form, with the different fractions condensing into differentreceiving flasks.

A short path will typically have 3 fractions-heads (terpenes and highvolatiles), main body (THC/CBD), and tails (high boiling pointcannabinoids).

The term “Thin Film Distillation” or “Wipe Film Distillation” refers toadding CBD crude oil, under vacuum, to the top of a heated verticalcylinder on a rotating plate. As the oil enters the cylinder (ajacketed, chilled condensing head), it encounters the rotating,specially designed wipers or rollers that create and renew a thin filmon the heated surface. A long, condenser in the middle of the wipers inthe evaporator body, cooled with recirculating fluid, condenses thevapor. Receiving vessels collect the distillate and the high temperatureresidue at the bottom. A recirculating heater maintains the temperatureof the feed container and outer jacketed wiped film evaporator body.Refrigerated circulators cool the condenser and cold trap.

Optimizing the feed rate, vacuum, and temperatures is essential to yieldthe desired component composition in the distillate. This method reducesthe exposure time of the oil. With a wiped film extraction, two passesthrough the system are required to achieve a distillate. As indistillation, wiped film strips the crude of low boiling point compoundsfirst, for example, terpenes and leftover volatiles. Then, during thesecond pass, the residue is run again to achieve the final CBDdistillate.

The term “hexanes” refers to mixed isomers of hexane used as a solvent.The boiling point of hexanes is 68-70 degrees Celsius.

The term “verification” or “compliance” refers to quantitative methodsfor ensuring a level of less than 0.3% Δ9-THC of the starting material,the reaction intermediates and reaction mixtures, the crude Δ8-THC oil,the clear Δ8-THC distillate, and the highly pure Δ8-THC oil.

Quantitative compliance verification methods contemplated as within thescope of the invention include, without limitation, a method selectedfrom the group consisting of post decarboxylation, HPLC, gaschromatography (GC), GC coupled with mass spectrometry (MS), GC coupledwith flame ionization detection (FID), HPLC with MS, HPLC withultraviolet (UV) absorbance, HPLC with diode array detection (DAD),HPLC-electrospray ionization-quadrupole time of flight (ESI-qTOF),HPLC-MS/MS, ultra-performance liquid chromatography (UPLC), UPLC-qTOF,matrix assisted laser desorption ionization mass spectrometry(MALDI-MS), thin layer chromatography (TLC), Fourier transform infraredspectroscopy (FTIR), and nuclear magnetic resonance spectrometry (NMR).

EXAMPLES

The invention will now be described by means of examples, although theinvention is not limited to these examples.

TABLE 1 Summary, Examples of Conversion of CBD to Δ8-THC Summary ofExamples Catalyst-to- Temp Solvent Catalyst solvent % Time ° C. Δ8 Δ9CBD Inventive Toluene P-Tosic 2.6 120 70 99.73 N/D N/D Example 1Comparative Toluene P-Tosic 2.6 120 100 73.59 N/D N/D Example 2Comparative Toluene P-Tosic 1 1440 100 87.01 N/D N/D Example 3Comparative Toluene P-Tosic 1 2880 100 88.13 9.18 N/D Example 4Comparative Toluene P-Tosic 20 35 100 88.28 7.98 N/D Example 5Comparative Toluene P-Tosic 20 90 100 84.88 4.51 N/D Example 6Comparative Ethanol P-Tosic 3 120/30 30/60 3.20 2.49 89.43 Example 7Comparative DCE ZnCl2 250 1440 80 56.01 18.92 N/D Example 8 ComparativeDCE ZnCl2 200 1440 80 62.13 30.55 N/D Example 9 Comparative DCE ZnCl2200 720 80 14.36 27.73 40.41 Example 10

Example 1—a Preferred Embodiment

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (130 g)was introduced to the reaction vessel. The mixture was refluxed at 70°C. for 120 minutes, although other time periods may be used, asdiscussed in alternative embodiments. The solution was then quenchedwith aqueous 10% NaHCO3, then with purified water, and evaporated. Thecollected crude oil showed the presence of 91.68% Δ8-THC by HPLC. Thisextract was then loaded into a distillation unit and purified throughdistillation. Raschig rings were used in the distillation heads toincrease purity. The completed residue was clear and stable at roomtemperature. The collected distilled oil showed the presence of 99.73%Δ8-THC by HPLC. An example of an essentially pure Δ8-THC by HPLC isshown in FIG. 1

In example 1, CBD isolate may have a non-limiting molar mass of 314.47g/mol with 5000 g equivalent to about 15.90 moles. Toluene may have amolar mass of 92.14 g/mol, and 25 liters of toluene at a density of 0.87g/mL is about 21750 g, and is equivalent to about 236.05 moles.P-toluenesulfonic acid monohydrate has a molar mass of about 172.2g/mol, and 130 g of p-tosic is equivalent to about 0.755 moles.

The calculated mass fraction of CBD to toluene to p-tosic is:

5000 g+21750 g+130 g=26880 g, or 18.60%.+80.92%+0.48%, respectively.

The calculated weight/weight ratios of grams solute in grams solvent is:

5000 g CBD isolate in 21750 g toluene=22.99 wt %

130 g p-tosic in 21750 g toluene=0.598 wt %

The calculated mole fraction is:

15.9 mol CBD isolate/252.705 mol total=6.29% (mole fraction),

236.5 mol toluene/252.705 mol total=93.41% (mole fraction), and 0.755mol p-tosic/252.705 mol total=0.299% (mole fraction).

Comparative Examples

Following are some comparative examples, i.e. failures, that show thatonly a variation of the process parameters will unexpectedly result in afailed product. Decreasing or increasing the % of the catalyst willchange the amount of the Δ8-THC and the Δ9-THC in the final product.This is critical because anything above 0.3% Δ9-THC, by law, is anon-compliant product and must be destroyed. Similarly, changing thereflux time will change the amount of the Δ8-THC and the Δ9-THC in thefinal product. And changing the reflux temperature will change theamount of the Δ8-THC and the Δ9-THC in the final product. Further,performing a thermal distillation versus a vacuum short-pathdistillation will degrade various cannabinoids and result in higherimpurities. And, letting the vacuum distillation run past the pointwhere solvent and volatile, low boiling point cannabinoids are removedrisks reducing yield of a Δ8-THC final product. Similarly, using only asingle distillation process, e.g. without using the wiped filmdistillation, will leave high boiling point cannabinoids as impurities.As stated, these specific process parameters are critical becauseanything above 0.3% Δ9-THC, by law, is a non-compliant product and mustbe destroyed.

Δ8-THC Process Remaining Δ9-THC Compliant

It is important to note that the inventive process starts with anindustrial hemp plant that is less than 0.3% Δ9-THC. The cannabidiol(CBD) extract obtained from the compliant hemp is processed to also haveless than 0.3% Δ9-THC. The next step of processing with an organic acid,e.g. p-toluenesulfonic acid, in a chemically-related and compatiblesolvent, e.g. toluene, followed by quenching with a neutralizingcompound, e.g. sodium bicarbonate, and washing with water, also yields acrude Δ8-THC oil having less than 0.3% Δ9-THC. Thus, the entire processstays Δ9-THC-compliant at each step. Further performing a short-pathvacuum distillation to remove the low temperature impurities ensuresthat the crude Δ8-THC oil produces a Δ8-THC distillate without allowingthe cannabidiol to isomerize to the unwanted and non-compliant Δ9-THC.Lastly, performing a wiped film distillation to remove the hightemperature impurities also ensures that the Δ8-THC distillate producesa highly pure Δ8-THC oil having >99% Δ8-THC by HPLC without allowing anyfurther isomerization to the unwanted and non-compliant Δ9-THC.

Example 2—Comparative Failure

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (130 g)was introduced to the reaction vessel. The mixture was refluxed at 100°C. for 120 minutes, although other time periods may be used, asdiscussed in alternative embodiments. The solution was then quenchedwith aqueous 10% NaHCO₃, then with water, and evaporated. The collectedcrude oil showed the presence of 65.61% Δ8-THC by HPLC. This extract wasthen loaded into a distillation unit and purified through distillation.The completed residue was a light yellow color and stable at roomtemperature.

The collected distilled oil showed the presence of 73.59% Δ8-THC byHPLC.

Example 3—Comparative Failure

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (50 g) wasintroduced to the reaction vessel. The mixture was refluxed for 1440minutes, although other time periods may be used, as discussed inalternative embodiments. The solution was then quenched with aqueous 10%NaHCO3, then with water, and evaporated. The collected crude oil showedthe presence of 81.27% Δ8-THC by HPLC. This extract was then loaded intoa distillation unit and purified through distillation.

The completed residue was clear and stable at room temperature. Thecollected distilled oil showed the presence of 87.01% Δ8-THC by HPLC.

Example 4—Comparative Failure

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (50 g) wasintroduced to the reaction vessel. The mixture was refluxed for 2880minutes, although other time periods may be used, as discussed inalternative embodiments. The solution was then quenched with aqueous 10%NaHCO₃, then with water, and evaporated. The collected crude oil showedthe presence of 76.38% Δ8-THC but also had 5.26% Δ9-THC by HPLC. Thisextract was then loaded into a distillation unit and purified throughdistillation. The completed residue was clear and stable at roomtemperature. The collected distilled oil showed the presence of 88.13%Δ8-THC and 9.18% Δ9-THC by HPLC.

Example 5—Comparative Failure

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (1000 g)was introduced to the reaction vessel. The mixture was refluxed at 100°C. for 35 minutes, although other time periods may be used, as discussedin alternative embodiments. The solution was then quenched with aqueous10% NaHCO3, then with water, and evaporated. The collected crude oilshowed the presence of 79.31% Δ8-THC but also had 4.32% Δ9-THC by HPLC.This extract was then loaded into a distillation unit and purifiedthrough distillation. The completed residue was a light yellow color andstable at room temperature. The collected distilled oil showed thepresence of 88.28% Δ8-THC and 7.98% Δ9-THC by HPLC.

Example 6—Comparative Failure

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (1000 g)was introduced to the reaction vessel. The mixture was refluxed at 100°C. for 90 minutes, although other time periods may be used, as discussedin alternative embodiments. The solution was then quenched with aqueous10% NaHCO₃, then with water, and evaporated. The collected crude oilshowed the presence of 74.90% Δ8-THC but also had 2.92% Δ9-THC by HPLC.This extract was then loaded into a distillation unit and purifiedthrough distillation. The completed residue was a light yellow color andstable at room temperature. The collected distilled oil showed thepresence of 84.88% Δ8-THC and 4.51% Δ9-THC by HPLC.

Example 7—Comparative Failure

CBD isolate (5000 g) was added and dissolved into ethanol (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (150 g)was introduced to the reaction vessel. The mixture was refluxed at 30°C. for 120 minutes, then refluxed at 60° C. for 30 minutes althoughother time periods may be used, as discussed in alternative embodiments.The solution was then quenched with aqueous 10% NaHCO₃, then with water,and evaporated. The collected crude oil showed the presence of 2.92%Δ8-THC but also had 2.45% Δ9-THC and 85.87% CBD by HPLC. This extractwas then loaded into a distillation unit and purified throughdistillation. The completed residue was a light yellow color and stableat room temperature. The collected distilled oil showed the presence of3.20% Δ8-THC, 2.49% Δ9-THC, and 89.43% CBD by HPLC.

Example 8—Comparative Failure

CBD isolate (5000 g) was added and dissolved into dichloroethane (25 L)to create a homogenized mixture. The solution was loaded into thereaction vessel and heat was added. Zinc Chloride (12500 g) wasintroduced to the reaction vessel. The mixture was refluxed at 80° C.for 1440 minutes, although other time periods may be used, as discussedin alternative embodiments. The solution was then quenched with aqueous10% NaHCO₃, then with water, and evaporated. The collected crude oilshowed the presence of 49.54% Δ8-THC but also had 15.25% Δ9-THC by HPLC.This extract was then loaded into a distillation unit and purifiedthrough distillation. The completed residue was a light yellow color andstable at room temperature. The collected distilled oil showed thepresence of 56.01% Δ8-THC and 18.92% Δ9-THC by HPLC.

Example 9—Comparative Failure

CBD isolate (5000 g) was added and dissolved into dichloroethane (25 L)to create a homogenized mixture. The solution was loaded into thereaction vessel and heat was added. Zinc Chloride (10000 g) wasintroduced to the reaction vessel. The mixture was refluxed at 80° C.for 1440 minutes, although other time periods may be used, as discussedin alternative embodiments. The solution was then quenched with aqueous10% NaHCO3, then with water, and evaporated. The collected crude oilshowed the presence of 54.20% Δ8-THC but also had 25.93% Δ9-THC by HPLC.This extract was then loaded into a distillation unit and purifiedthrough distillation. The completed residue was a light yellow color andstable at room temperature. The collected distilled oil showed thepresence of 62.13% Δ8-THC and 30.55% Δ9-THC by HPLC.

Example 10—Comparative Failure

CBD isolate (5000 g) was added and dissolved into dichloroethane (25 L)to create a homogenized mixture. The solution was loaded into thereaction vessel and heat was added. Zinc Chloride (10000 g) wasintroduced to the reaction vessel. The mixture was refluxed at 80° C.for 720 minutes, although other time periods may be used, as discussedin alternative embodiments. The solution was then quenched with aqueous10% NaHCO3, then with water, and evaporated. The collected crude oilshowed the presence of 12.20% Δ8-THC but also had 24.09% Δ9-THC and37.84% CBD by HPLC. This extract was then loaded into a distillationunit and purified through distillation. The completed residue was alight yellow color and stable at room temperature. The collecteddistilled oil showed the presence of 14.36% Δ8-THC, 27.73% Δ9-THC, and40.41% CBD by HPLC.

Example 11—Another Preferred Embodiment

CBD isolate (5000 g) was added and dissolved into toluene (25 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added.

P-toluenesulfonic acid monohydrate (130 g) was introduced to thereaction vessel. The mixture was refluxed at 70° C. for 120 minutes,although other time periods may be used, as discussed in alternativeembodiments. The solution was then quenched with aqueous 10% NaHCO₃,then with purified water, and evaporated. After the majority of thesolvent has been evaporated, the collected crude oil showed the presenceof 91.41% Δ8-THC by HPLC. The crude is then loaded into a short pathvacuum distillation system. The temperature is adjusted until theresidual solvent and terpenes are collected. Once the clear distillatestarts to condense, the system is turned off, and the remaining crude isloaded into a wiped film distillation unit.

Parameters are set, and the material is run through the system in a muchmore efficient manner to establish the industrial scale processingdesired by large manufacturers. Raschig rings were used in the shortpath distillation head to increase purity. The completed residue wasclear and stable at room temperature. The collected distilled oil showedthe presence of 99.68% Δ8-THC by HPLC.

Example 12—Another Preferred Embodiment

CBD isolate (50 kg) was added and dissolved into toluene (250 L) tocreate a homogenized mixture. The solution was loaded into the reactionvessel and heat was added. P-toluenesulfonic acid monohydrate (1300 g)was introduced to the reaction vessel. The mixture was refluxed at 70°C. for 120 minutes, although other time periods may be used, asdiscussed in alternative embodiments. The solution was then quenchedwith aqueous 10% NaHCO₃, then with purified water, and evaporated. Afterthe majority of the solvent has been evaporated, the collected crude oilshowed the presence of greater than 90% Δ8-THC by HPLC. The crude isthen loaded into a short path vacuum distillation system. Thetemperature is adjusted until the residual solvent and terpenes arecollected. Once the clear distillate starts to condense, the system isturned off, and the remaining crude is loaded into a wiped filmdistillation unit. Parameters are set, and the material is run throughthe system in a much more efficient manner to establish the industrialscale processing desired by large manufacturers.

Raschig rings were used in the short path distillation head to increasepurity. The completed residue was clear and stable at room temperature.The collected distilled oil showed the presence of greater than 99%Δ8-THC by HPLC.

Example 13—Compliance Verification Embodiment

Crude Δ8-THC oil having about 73.59-99.73% Δ8-THC by HPLC and less than0.3% Δ9-THC by HPLC is obtained using a process described herein. Vacuumdistillation of the crude Δ8-THC oil with a short path vacuumdistillation system to obtain a clear Δ8-THC distillate is followed by awiped film distillation of the clear Δ8-THC distillate to obtain aΔ8-THC oil having >99% Δ8-THC by HPLC, optionally followed by repeatingthe wiped film distillation a second time. The step of verifyingcompliance of less than 0.3% Δ9-THC of the crude Δ8-THC oil, the clearΔ8-THC distillate and/or Δ8-THC oil is performed at one or more pointsin the process using a verification method selected from the groupconsisting of post decarboxylation, HPLC, gas chromatography (GC), GCcoupled with mass spectrometry (MS), GC coupled with flame ionizationdetection (FID), HPLC with MS, HPLC with ultraviolet (UV) absorbance,HPLC with diode array detection (DAD), HPLC-electrosprayionization-quadrupole time of flight (ESI-qTOF), HPLC-MS/MS,ultra-performance liquid chromatography (UPLC), UPLC-qTOF, matrixassisted laser desorption ionization mass spectrometry (MALDI-MS), thinlayer chromatography (TLC), Fourier transform infrared spectroscopy(FTIR), and nuclear magnetic resonance spectrometry (NMR).

Pharmaceutical Compositions/Medicaments

Any of the compositions of the invention may be converted usingcustomary methods into pharmaceutical compositions and medicaments. Thepharmaceutical composition and medicaments contain the composition ofthe invention either alone or together with other active substances.Such pharmaceutical compositions and medicaments can be for oral,topical, rectal, parenteral, local, or inhalant use. They are thereforein solid or semisolid form, for example oils, drops, lotions, balm,pills, tablets, creams, gelatin capsules, capsules, suppositories, softgelatin capsules, gels, foams, powders, and formulated for internal use.For parenteral uses, those forms for intramuscular or subcutaneousadministration can be used, or forms for infusion or intravenousinjection can be used, and can therefore be prepared as solutions of thecompositions and medicaments or as powders of the active compositions tobe mixed with one or more pharmaceutically acceptable excipients ordiluents, suitable for the aforesaid uses and with an osmolarity that iscompatible with the physiological fluids. For local use, thosepreparations in the form of creams or ointments for topical use or inthe form of sprays may be considered; for inhalant uses, preparations inthe form of sprays, for example nose sprays, may be considered.Preferably, the composition and medicaments is administered topically ororally.

Any of the pharmaceutical compositions and medicaments can be preparedby per se known methods for the preparation of pharmaceuticallyacceptable compositions which can be administered to patients, and suchthat an effective quantity of the active substance is combined in amixture with a pharmaceutically acceptable vehicle. Suitable vehiclesare described, for example, in Remington's Pharmaceutical Sciences (NackPublishing Company, Easton, Pa., USA 1985).

On this basis, the pharmaceutical compositions and medicaments include,albeit not exclusively, the composition of the invention in associationwith one or more pharmaceutically acceptable vehicles or diluents, andare contained in buffered solutions with a suitable pH and iso-osmoticwith the physiological fluids.

Any of the compositions and medicaments are indicated as therapeuticagents either alone or in conjunction with other therapeutic agents orother forms of treatment. For example, in the case of skin care orcosmetic use, or for nausea, anxiety, stress, chronic pain, acute painand used as an appetite stimulant. The compositions and agents of theinvention are intended for administration to humans or animals.

Example—Oral Formulation

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is homogenized with a dietaryoil, an optional secondary solvent and/or surfactant at 0.1-10% w/v, andan optional anti-oxidant. An optional sweetener or flavorant may beadded. An oral formulation of pure D8-THC is obtained. The dietary oilmay comprise medium chain (C8-C12) and long chain (C10-C22) dietarytriglycerides selected from the group consisting of caprylictriglyceride, capric triglyceride, lauric triglyceride, myristictriglyceride, palmitic triglyceride, stearic triglyceride, oleictriglyceride, linoleic triglyceride, gamma linoleic triglyceride,ricinoleic triglyceride, arachidic triglyceride, behenic triglyceride,and derivatives and mixtures thereof. The dietary oil may also comprise,alone or in combination with MCT or LCT, sesame oil, vitamin E, soybeanoil, vegetable oil, corn oil, olive oil, peanut oil, coconut oil,palmseed oil, and mixtures thereof. The optional secondary solvents areselected from ethanol, glycerol, propylene glycol, and polyethyleneglycols.

Example—Oral Formulation

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is formulated into a tincture,a gummi, or fast melt tab, by mixing a dietary wax, an optionalsecondary dietary oil, an optional secondary solvent and/or surfactantat 0.1-10% w/v, and an optional anti-oxidant. An optional sweetener orflavorant may be added. An oral formulation of pure D8-THC is obtained.The dietary wax may comprise bees wax, plant waxes, very long chainfatty acid waxes, and mixtures thereof. The dietary oil may comprisemedium chain (C8-C12) and long chain (C10-C22) dietary triglyceridesselected from the group consisting of caprylic triglyceride, caprictriglyceride, lauric triglyceride, myristic triglyceride, palmitictriglyceride, stearic triglyceride, oleic triglyceride, linoleictriglyceride, gamma linoleic triglyceride, ricinoleic triglyceride,arachidic triglyceride, behenic triglyceride, and derivatives andmixtures thereof. The dietary oil may also comprise, alone or incombination with MCT or LCT, sesame oil, vitamin E, soybean oil,vegetable oil, corn oil, olive oil, peanut oil, coconut oil, palmseedoil, and mixtures thereof. The optional secondary solvents are selectedfrom a very long chain fatty alcohol (C24-C34), ethanol, glycerol,propylene glycol, and polyethylene glycols.

Example—Oral Formulation

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is formulated into a tincture,a gummi, or fast melt tab, by mixing with sesame oil and ethanol. Anoral formulation of pure D8-THC is obtained.

Topical Formulations

In preferred embodiments, the present compositions can additionallycomprise at least one skin conditioning agent. In this regard, thepresent compositions preferably contain about 1% to about 15% by weight,and more preferably from about 5% to about 10% of at least one agent.The skin conditioning agent can help provide the softening, smoothing,lubricating, and skin conditioning features of the presently preferredcompositions.

Preferred non-limiting examples of skin conditioning agents useful inthe present compositions include petrolatum, red petrolatum, whitepetrolatum, liquid petrolatum, semi-solid petrolatum, light mineral oil,heavy mineral oil, white mineral oil, mineral oil alcohols, calamine,derivatives thereof, and mixtures thereof.

Organosiloxane

Any of the presently preferred compositions can further comprise atleast one organosiloxane. Organosiloxanes useful in the presentcompositions can be volatile or nonvolatile, including but not limitedto polyalkylsilicones, cyclic polyalkylsiloxanes, polydialkylsiloxanes,polydiarylsiloxanes, polyalkarylsiloxanes, or cyclomethicones.

Preferred polyalkylsiloxanes useful in this regard have a viscosity offrom about 0.5 to about 100,000 centistokes at 25.degree. C., and morepreferably have a viscosity of less than 500 centistokes at 25.degree.C.

Aqueous Solvent

Any of the present compositions additionally comprise an aqueoussolvent. Preferably the aqueous solvent is present in the instantcompositions from about 50% to about 95% by weight, and more preferablyfrom about 60% to about 90% by weight.

Emollient

Certain of the presently preferred compositions can additionallycomprise at least one emollient. The present compositions may containabout 0.01% to about 5% by weight, and more preferably from about 0.1%to about 1% by weight of an emollient.

Dermatologically Acceptable Excipients

Any of the preferred compositions discussed herein can additionallycomprise at least one dermatologically acceptable excipient commonlyknown to those of ordinary skill in the art as useful in topicalcompositions. Preferred, non-limiting examples of dermatologicallyacceptable excipients useful in these compositions are those selectedfrom the group consisting of moisturizers, preservatives, gellingagents, colorants or pigments, antioxidants, radical scavengers,emulsifiers, pH modifiers, chelating agents, penetration enhancers,derivatives thereof, and mixtures thereof.

Moisturizers

Any of the presently preferred compositions may optionally furthercontain at least one moisturizer. Preferably, the presently preferredcompositions can comprise about 0.01% to about 10% by weight of at leastone moisturizer. Preferred non-limiting examples of moisturizers thatcan optionally be included in these compositions include glycerin,pentylene glycol, butylene glycol, polyethylene glycol, sodiumpyrrolidone carboxylate, alpha-hydroxy acids, beta-hydroxy acids,polyhydric alcohols, ethoxylated and propoxylated polyols, polyols,polysaccharides, panthenol, hexylene glycol, propylene glycol,dipropylene glycol, sorbitol, derivatives thereof, and mixtures thereof.

Preservatives

Any of the presently preferred compositions may optionally furthercontain at least one preservative. Preferred non-limiting examples ofpreservatives that can optionally be included in these compositionsinclude benzyl alcohol, methyl paraben, ethyl paraben, derivativesthereof, and mixtures thereof. A particularly preferred preservative inthis regard is benzyl alcohol or a derivative thereof. Additionally, thepreservative is preferably present in an amount of about 0.1% to about2.5% by weight of the overall weight of the composition.

Gelling Agents

Any of the presently preferred compositions may optionally furthercontain a gelling agent. Preferred non-limiting examples of gellingagents that can optionally be included in these compositions includevarious cellulose agents, such as cellulosic polymers, methylcellulose,hydroxyethylcellulose, hydroxypropylcellulose, andhydroxypropylmethylcellulose. Additional, non-limiting examples ofgelling agents include gum arabic, gum tragacanth, locust bean gum, guargum, xanthan gum, cellulose gum, sodium carbomer, carbomer, polyacrylicpolymers, derivatives thereof, and mixtures thereof. Other suitablegelling agents which may be useful in the present compositions includeaqueous gelling agents, such as neutral, anionic, and cationic polymers,derivatives thereof, and mixtures thereof. Exemplary polymers which maybe useful in the preferred compositions in this regard include carboxyvinyl polymers, such as carboxypolymethylene. Additionally preferredgelling agents include Carbopol® and Carbomer® polymers (i.e.polyacrylic polymers) such as is available from Noveon Inc., Cleveland,Ohio. The gelling agent is preferably present in the instantcompositions in an amount of from about 0.01% to about 10%, morepreferably from about 0.1% to about 5%, and most preferably from about0.1% to about 2%, by weight.

Anti-Oxidants

Any of the presently preferred compositions may optionally furthercontain at least one anti-oxidant. Preferably, the presently preferredcompositions can comprise about 0.1% to about 5% by weight of at leastone anti-oxidant. Preferred non-limiting examples of antioxidants thatcan optionally be included in these compositions include ascorbic acid,ascorbyl esters of fatty acids, magnesium ascorbyl phosphate, sodiumascorbyl phosphate, ascorbyl sorbate, tocopherol, tocopherol sorbate,tocopherol acetate, butylated hydroxy benzoic acid, thioglycolates,persulfate salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylicacid, lipoic acid, gallic acid, propyl gallate, uric acid, sorbic acid,lipoic acid, amines, N,N-diethylhydroxylamine, N-acetyl-L-cysteine,amino-guanidine, sulfhydryl compounds, glutathione, dihydroxy fumaricacid, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid,bioflavonoids, curcumin, lysine, 1-methionine, proline, superoxidedismutase, silymarin, tea extracts, grape skin/seed extracts, melanin,rosemary extracts, derivatives thereof, and mixtures thereof.

Emulsifiers

Any of the presently preferred compositions may optionally furthercontain an emulsifier. Preferably, the presently preferred compositionscan comprise about 0.05% to about 15% by weight, and more preferablyfrom about 0.5% to about 10% by weight of at least one emulsifier.Preferred, non-limiting examples of specific emulsifiers useful in thisregard include glycol esters, fatty acids, fatty alcohols, fatty acidglycol esters, fatty esters, fatty ethers, esters of glycerin, esters ofpropylene glycol, fatty acid esters of polyethylene glycol, fatty acidesters of polypropylene glycol, esters of sorbitol, esters of sorbitananhydrides, carboxylic acid copolymers, esters and ethers of glucose,ethoxylated ethers, ethoxylated alcohols, alkyl phosphates,polyoxyethylene fatty ether phosphates, fatty acid amides, acyllactylates, soaps, polyethylene glycol 20 sorbitan monolaurate(polysorbate 20), polyethylene glycol 5 soya sterol, steareth-2,steareth-20, steareth-21, ceteareth-20, PPG-2 methyl glucose etherdistearate, ceteth-10, polysorbate 80, cetyl phosphate, potassium cetylphosphate, diethanolamine cetyl phosphate, polysorbate 60, glycerylstearate, PEG-8 stearate, PEG-100 stearate, derivatives thereof, andmixtures thereof.

pH Modifiers

Any of the presently preferred compositions may optionally furthercontain a pH modifier. Preferably, the presently preferred compositionscan comprise about 0.001% to about 1% by weight of a pH modifier.Preferred non-limiting examples of neutralizing pH modifiers that canoptionally be included in these compositions include inorganichydroxides, inorganic oxides, inorganic salts of weak acids, derivativesthereof, and mixtures thereof. Preferred, non-limiting examples ofinorganic hydroxides useful in this regard include ammonium hydroxide,alkali metal hydroxide, alkaline earth metal hydroxides, derivativesthereof, and mixtures thereof. Preferred inorganic hydroxides useful inthis regard include ammonium hydroxide, monovalent alkali metalhydroxides such as sodium hydroxide and potassium hydroxide, divalentalkali earth metal hydroxides such as calcium hydroxide and magnesiumhydroxide, derivatives thereof, and mixtures thereof. Preferred,non-limiting examples of inorganic oxides useful in this regard includemagnesium oxide, calcium oxide, derivatives thereof, and mixturesthereof. Preferred, non-limiting examples of inorganic salts of weakacids useful in this regard include ammonium phosphate (dibasic), alkalimetal salts of weak acids such as sodium acetate, sodium borate, sodiummetaborate, sodium carbonate, sodium bicarbonate, sodium phosphate(tribasic), sodium phosphate (dibasic), potassium carbonate, potassiumbicarbonate, potassium citrate, potassium acetate, potassium phosphate(dibasic), potassium phosphate (tribasic), alkaline earth metal salts ofweak acids such as magnesium phosphate and calcium phosphate,derivatives thereof, and mixtures thereof.

Chelating Agents

Any of the presently preferred compositions may optionally furthercontain a chelating agent. Preferably, the presently preferredcompositions can comprise about 0.01% to about 1% by weight of achelating agent. Preferred non-limiting examples of chelating agentsthat can optionally be included in these compositions include citricacid, isopropyl (mono) citrate, stearyl citrate, lecithin citrate,gluconic acid, tartaric acid, oxalic acid, phosphoric acid, sodiumtetrapyrophosphate, potassium monophosphate, sodium hexametaphosphate,calcium hexametaphosphate, sorbitol, glycine (aminoacetic acid), methylglucamine, triethanolamine (trolamine), EDTA, DEG(dihydroxyethylglycine), DPTA (diethylene triamine pentaacetic acid),NTA (Nitrilotriacetic Acid), HEDTA(N-(hydroxyethyl)-ethylenetriaminetriacetic acid), aminocarboxylates,dimercaperol (BAL), larixinic acid (Maltol), unidentate ligands(fluoride and cyanide ions), diphenylthiocarbazone, 0-phenanthroline,barium diphenylamine sulfonate, sodium glucoheptonate,8-hydroxyquinoline, olefin complexes (such as dicyclopentadienyl iron),porphyrins, phosphonates, pharmaceutically acceptable salts thereof,derivatives thereof, and mixtures thereof.

In addition to those enumerated above, any other pharmaceutically activeagent, occlusive skin conditioning agent, emollient, penetrationenhancer, organosiloxane, moisturizer, preservative, gelling agent,colorant or pigment, antioxidant, radical scavenger, emulsifier, pHmodifier, chelating agent, or other dermatologically acceptableexcipient commonly known to those of ordinary skill in the art as usefulin topical compositions is contemplated as useful in the compositionsdescribed herein. Further, any non-toxic, inert, and effective topicalcarrier may be used to formulate the compositions described herein.Well-known carriers used to formulate other topical therapeuticcompositions for administration to humans will be useful in thesecompositions. Examples of these components that are well known to thoseof skill in the art are described in The Merck Index, ThirteenthEdition, Budavari et al., Eds., Merck & Co., Inc., Rahway, N.J. (2001);the CTFA (Cosmetic, Toiletry, and Fragrance Association) InternationalCosmetic Ingredient Dictionary and Handbook, Tenth Edition (2004); andthe “Inactive Ingredient Guide”, U.S. Food and Drug Administration (FDA)Center for Drug Evaluation and Research (CDER) Office of Management, thecontents of which are hereby incorporated by reference in theirentirety. Examples of such useful pharmaceutically acceptableexcipients, carriers and diluents include distilled water, physiologicalsaline, Ringer's solution, dextrose solution, Hank's solution, and DMSO,which are among those preferred for use herein.

These additional other inactive components, as well as effectiveformulations and administration procedures, are well known in the artand are described in standard textbooks, such as Goodman and Gillman's:The Pharmacological Bases of Therapeutics, 8th Ed., Gilman et al. Eds.Pergamon Press (1990) and Remington's Pharmaceutical Sciences, 17th Ed.,Mack Publishing Co., Easton, Pa. (1990), both of which are incorporatedby reference herein in their entirety.

In another particularly preferred embodiment, the presently preferredpharmaceutical compositions are formulated in a lotion, cream, ointment,gel, suspension, emulsion, foam, aerosol, or other pharmaceuticallyacceptable topical dosage form.

Example—Topical Transdermal Composition

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is formulated into atransdermal formulation by mixing pure D8-THC with a transdermalformulation base, the transdermal formulation base comprising anemulsion formed from an aqueous phase and an oil phase, and anpenetration enhancer, an optional emulsifier, and an optional emollient.A topical transdermal D8-THC composition is thereby obtained.

Example—Topical Composition

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is formulated as a cream, anointment, foam, gel, lotion, ointment, paste, spray, or solution. Atopical >99% pure D8-THC composition having less than 0.3% D9-THC isthereby obtained.

The cream or ointment is a water-in-oil or oil-in-water emulsioncontaining less than 20% water, greater than 50% hydrocarbons, waxesand/or polyols, and using a surfactant to create a semi-solid,spreadable composition. The foam is a cream or ointment packaged in apressurized container and delivered with a gas.

Example—Topical Composition

A >99% pure D8-THC oil having less than 0.3% D9-THC is prepared, theD8-THC oil at a dosage of 5-14 mg/Kg/day is formulated as a topicalcomposition comprising: (i) >99% pure D8-THC oil having less than 0.3%D9-THC, and (ii) a carrier formulation comprising: a self-emulsifyingwax (i.e. glyceryl stearate, PEG-100 stearate), a polyol (glycerin), afatty alcohol (cetyl alcohol), a moisturizer (allantoin), a hydrocarbonmoisturizer/occlusive (petrolatum), an emulsifier (i.e. steareth-21), anantioxidant (tocopheryl acetate), and optionally a fragrance, astabilizer (xanthan gum), a skin conditioner (i.e dipotassiumglycyrrhizate), Aloe Barbadensis Leaf Juice, a surfactant(triethanolamine), an anti-inflammatory (i.e. bisabolol), and apreservative (disodium EDTA).

Any of the topical formulations herein may include a hydrocarbon base(“oleaginous”), such a white petrolatum or white ointment, an absorptionbase (water-in-oil) such as hydrophilic petrolatum or lanolin,water-removable base (oil-in-water) such as hydrophilic ointment, or awater-soluble base, such as polyethylene glycol ointment.

The topical formulation may also include a wax such as bees wax, plantwaxes, very long chain fatty acid waxes, and mixtures thereof, an oilsuch as medium chain (C8-C12) and long chain (C10-C22) triglycerides,and alone or in combination with MCT or LCT, sesame oil, vitamin E,soybean oil, vegetable oil, corn oil, olive oil, peanut oil, coconutoil, palmseed oil, and mixtures thereof. Any of the topical formulationsherein may include solvents are selected from a very long chain fattyalcohol (C24-C34), ethanol, glycerol, propylene glycol, and polyethyleneglycols. Any of the topical formulations herein may include apenetration enhancer such as ethoxydiglycol (i.e. transcutanol) or anequivalent.

Uses

As used herein, the terms “administering”, “administration”, and liketerms refer to any method which, in sound medical or cosmetic practice,delivers the composition to a subject in such a manner as to provide apositive effect on a dermatological disorder, condition, or appearance.The compositions are preferably administered such that they cover theentire area to be treated. “Direct administration” refers to any methodwhich, in sound medical or cosmetic practice, delivers the compositionto a subject without the use of another composition, delivery agent, ordevice. “Indirect administration” refers to any method which, in soundmedical or cosmetic practice, delivers the composition to a subject withthe use of at least one other composition, delivery agent, or device.

As used herein, the phrases an “effective amount” or a “therapeuticallyeffective amount” of an active agent or ingredient, or pharmaceuticallyactive agent or ingredient, which are synonymous herein, refer to anamount of the pharmaceutically active agent sufficient enough to have apositive effect on the area of application. Accordingly, these amountsare sufficient to modify the skin disorder, condition, or appearance tobe treated but low enough to avoid serious side effects, within thescope of sound medical or dermatological advice. A therapeuticallyeffective amount of the pharmaceutically active agent will cause asubstantial relief of symptoms when applied repeatedly over time.Effective amounts of the pharmaceutically active agent will vary withthe particular condition or conditions being treated, the severity ofthe condition, the duration of the treatment, the specific components ofthe composition being used, and like factors.

EQUIVALENTS

Various of the above-disclosed and other features and functions, oralternatives thereof, may be combined into many other different systemsor applications. Various presently unforeseen or unanticipatedalternatives, modifications, variations or improvements therein may besubsequently made by those skilled in the art, each of which is alsointended to be encompassed by the disclosed embodiments.

Having described embodiments for the invention herein, it is noted thatmodifications and variations can be made by persons skilled in the artin light of the above teachings. It is therefore to be understood thatchanges may be made in the particular embodiments of the inventiondisclosed which are within the scope and spirit of the invention asdefined by the appended claims. Having thus described the invention withthe details and particularity required by the patent laws, what isclaimed and desired protected by Letters Patent is set forth in theappended claims.

The invention claimed is:
 1. A composition, comprising a >99% pureΔ8-tetrahydrocannabinol (THC) oil having less than 0.3% Δ9-THC, whereinthe >99% pure Δ8-THC oil is a distillate having residual solvent andvolatile cannabidiol impurities removed by vacuum distillation, andhaving high temperature cannabinoid impurities with a non-vacuum boilingpoint higher than 180° C. removed by wiped film distillation, whereinsaid distillate is a reaction product of a cannabidiol extract fromindustrial hemp having less than 0.3% Δ9-THC, wherein the composition isformulated for oral, topical, rectal, parenteral, local, or inhalantuse, and is a form selected from the group consisting of as an oil,drop, lotion, balm, pill, tablet, cream, gelatin capsule, capsule,suppository, soft gelatin capsule, gel, foams, powder, ointment, spray,and inhalant, and wherein said topical composition having (i) >99% pureD8-THC oil having less than 0.3% D9-THC, the D8-THC oil at a dosage of5-14 mg/Kg/day, and (ii) a carrier formulation comprising: aself-emulsifying wax, a polyol, a fatty alcohol, a moisturizer, ahydrocarbon moisturizer/occlusive, an emulsifier, an antioxidant, andoptionally a fragrance, a stabilizer, a skin conditioner, AloeBarbadensis Leaf Juice, a surfactant, an anti-inflammatory, and apreservative wherein the self-emulsifying wax is selected from glycerylstearate and PEG-100 stearate, the polyol is glycerin, the fatty alcoholis cetyl alcohol, the moisturizer is allantoin, the hydrocarbonmoisturizer/occlusive is petrolatum, the emulsifier is steareth-21, theantioxidant is tocopheryl acetate, the stabilizer is xanthan gum, theskin conditioner is dipotassium glycyrrhizate, the surfactant istriethanolamine, the anti-inflammatory is bisabolol, and thepreservative is disodium EDTA.
 2. The composition according to claim 1,comprising a >99% pure D8-THC oil having less than 0.3% D9-THC, theD8-THC oil at a dosage of 5-14 mg/Kg/day is homogenized with a dietaryoil, an optional secondary solvent and/or surfactant at 0.1-10% w/v, andan optional anti-oxidant, having an optional sweetener or flavorant, andformulated as an oral formulation.
 3. The composition according to claim1, wherein a >99% pure D8-THC oil having less than 0.3% D9-THC isprepared as an oral formulation, the D8-THC oil at a dosage of 5-14mg/Kg/day is formulated into a tincture, a gummi, or fast melt tab, bymixing a dietary wax, an optional secondary dietary oil, an optionalsecondary solvent and/or surfactant at 0.1-10% w/v, and an optionalanti-oxidant, an optional sweetener or flavorant may be added, thedietary wax may comprise bees wax, plant waxes, very long chain fattyacid waxes, and mixtures thereof, the dietary oil may comprise C₈-C₁₂and C₁₀-C₂₂ dietary triglycerides selected from the group consisting ofcaprylic triglyceride, capric triglyceride, lauric triglyceride,myristic triglyceride, palmitic triglyceride, stearic triglyceride,oleic triglyceride, linoleic triglyceride, gamma linoleic triglyceride,ricinoleic triglyceride, arachidic triglyceride, behenic triglyceride,and mixtures thereof, the dietary oil may also comprise, alone or incombination with MCT or LCT, sesame oil, vitamin E, soybean oil,vegetable oil, corn oil, olive oil, peanut oil, coconut oil, palmseedoil, and mixtures thereof, the optional secondary solvents are selectedfrom a very long chain fatty alcohol C₂₄-C₃₄, ethanol, glycerol,propylene glycol, and polyethylene glycols.
 4. The composition accordingto claim 1, comprising an oral formulation having >99% pure D8-THC oilhaving less than 0.3% D9-THC, the D8-THC oil at a dosage of 5-14mg/Kg/day is formulated into a tincture, a gummi, or fast melt tab, bymixing with sesame oil and ethanol.
 5. The composition according toclaim 1, formulated as a topical transdermal composition having a >99%pure D8-THC oil having less than 0.3% D9-THC, the D8-THC oil at a dosageof 5-14 mg/Kg/day is formulated into a transdermal formulation by mixingpure D8-THC with a transdermal formulation base, the transdermalformulation base comprising an emulsion formed from an aqueous phase andan oil phase, and an penetration enhancer, an optional emulsifier, andan optional emollient, to obtain a topical transdermal D8-THCcomposition.
 6. The composition according to claim 1, formulated as atopical composition having >99% pure D8-THC oil having less than 0.3%D9-THC, the D8-THC oil at a dosage of 5-14 mg/Kg/day is formulated as acream, an ointment, foam, gel, lotion, ointment, paste, spray, orsolution, to obtain a topical >99% pure D8-THC composition having lessthan 0.3% D9-THC, the cream or ointment is a water-in-oil oroil-in-water emulsion containing less than 20% water, greater than 50%hydrocarbons, waxes and/or polyols, and using a surfactant to create asemi-solid, spreadable composition, the foam is a cream or ointmentpackaged in a pressurized container and delivered with a gas.
 7. Thecomposition according to claim 1, wherein the Cannabinoid extract is CBDcrude, CBD isolate or CBD distillate, refluxed in toluene andp-toluenesulfonic acid monohydrate at 50 to 100° C. for 60 to 180minutes, with a dilution ratio of the Cannabinoid extract to the tolueneis 3 to 6 on a weight basis, to obtain a Δ8-THC oil.
 8. The compositionaccording to claim 1, wherein the Cannabinoid extract from industrialhemp having less than 0.3% is CBD crude, CBD isolate or CBD distillate,refluxed in toluene and p-toluenesulfonic acid monohydrate at 70° C. for120 minutes, with a dilution ratio of the Cannabinoid extract to thetoluene is 3 to 6 on a weight basis, and quenched in aqueous sodiumbicarbonate 10%, to obtain a Δ8-THC oil.